Efficacy of Intrathecal Fentanyl for Cesarean Delivery: A Systematic Review and Meta-analysis of Randomized Controlled Trials With Trial Sequential Analysis

Abstract

BACKGROUND: Fentanyl and morphine are the 2 most commonly added opioids to bupivacaine for spinal anesthesia during cesarean delivery. Numerous clinical trials have assessed efficacy and safety of different doses of fentanyl added to intrathecal bupivacaine for spinal anesthesia, yet its benefit, harm, and optimal dose remain unclear. This study aimed to systematically review the evidence of the efficacy of fentanyl when added to intrathecal bupivacaine alone and when added to bupivacaine with morphine for spinal anesthesia during cesarean delivery. METHODS: Key electronic databases (PubMed, Embase, and Cochrane Library) were searched for randomized controlled trials in the cesarean delivery population. The primary outcome was the failure rate of spinal anesthesia, as assessed by the need for either conversion to general anesthesia or intraoperative analgesic supplementation. Two reviewers independently extracted the data using a standardized electronic form. Results are expressed as relative risks or mean differences with 95% CIs. RESULTS: Seventeen randomized controlled clinical trials (most judged as low or unclear risk of bias) with 1064 participants provided data for the meta-analysis. Fentanyl added to intrathecal bupivacaine alone reduced the need for intraoperative supplemental analgesia (relative risk, 0.18; 95% CI, 0.11–0.27; number needed to treat, 4) and the incidence of nausea/vomiting (relative risk, 0.41; 95% CI, 0.24–0.70; number needed to treat, 6.5), with longer time to first postoperative analgesia request (mean difference, 91 minutes; 95% CI, 69–113). No difference was observed regarding the need for conversion to general anesthesia (relative risk, 0.67; 95% CI, 0.12–3.57), the incidence of hypotension, the onset of sensory block, or the duration of motor block. However, the addition of intrathecal fentanyl was associated with higher incidence of intraoperative pruritus (relative risk, 5.89; 95% CI, 2.07–16.79; number needed to harm, 13.5). The inclusion of fentanyl to intrathecal bupivacaine–morphine compared to intrathecal bupivacaine–morphine alone conferred a similar benefit, with a significantly reduced need for intraoperative supplemental analgesia (relative risk, 0.16; 95% CI, 0.03–0.95; number needed to treat, 9). Analysis using a funnel plot indicated a possibility of publication bias in included studies. CONCLUSIONS: Current evidence suggests a benefit of using fentanyl as both an additive to intrathecal bupivacaine alone and to intrathecal bupivacaine combined with morphine for cesarean delivery under spinal anesthesia. The possibility of publication bias, small sample size, and high risk of bias in some of the included studies warrant treating the results with caution.

Comparison of intrathecal fentanyl and buprenorphine as an adjuvant to 0.5% hyperbaric bupivacaine for spinal anesthesia

“…Opioids are still currently being used as adjuvants to intrathecal blocks as side effects are minimal, and they can be safely used in the elderly as well as pregnant patients and ease of availability makes them a practical choice. [ 17 18 19 20 21 22 23 24 25 26 27 ] Previous systematic reviews have evaluated the safety and efficacy of intrathecal opioids (Fentanyl) as adjuvants for spinal anesthesia. [ 17 18 19 ] A study conducted by Wang and et al on the effects of intrathecal bupivacaine and bupivacaine plus fentanyl in elderly patients undergoing total hip arthroplasty showed that although the quality of anesthesia was the same, the fentanyl group showed less use of ephedrine for stable hemodynamics and a longer duration for postoperative analgesic use.…”

“…[ 17 18 19 20 21 22 23 24 25 26 27 ] Previous systematic reviews have evaluated the safety and efficacy of intrathecal opioids (Fentanyl) as adjuvants for spinal anesthesia. [ 17 18 19 ] A study conducted by Wang and et al on the effects of intrathecal bupivacaine and bupivacaine plus fentanyl in elderly patients undergoing total hip arthroplasty showed that although the quality of anesthesia was the same, the fentanyl group showed less use of ephedrine for stable hemodynamics and a longer duration for postoperative analgesic use. [ 19 ] Ravindran et al studied two doses of intrathecal buprenorphine as an adjuvant to 0.5% hyperbaric bupivacaine for cesarean sections and concluded that the addition of 60 mcg provided longer duration of postoperative analgesia as compared to 45 mcg and reported no side effects on mother as well as fetus.…”

Incidence and Effect of Intrathecal Fentanyl Use in Spinal Anesthesia for Cesarean Deliveries in the Community Setting: A Single-Center Observational Retrospective Study

“…2 A 2020 meta-analysis that included 14 randomized controlled trials with 694 patients undergoing cesarean delivery with spinal anesthesia showed that 17 of 370 patients (4.6%) who received intrathecal fentanyl with bupivacaine required systemic anesthetic adjunct medication compared to 96 of 324 (29.6%) patients who received only bupivacaine, a result that was statistically significant (P<0.001). 5 Increased pain is a potential consequence of using lower doses of intrathecal bupivacaine for cesarean deliveries performed with spinal anesthesia. A 2011 meta-analysis showed a higher risk for systemic anesthetic adjunct supplementation in patients who received <8 mg of subarachnoid bupivacaine for cesarean delivery with spinal anesthesia compared to patients who received >8 mg. 6 Studies published in 2004 and 2017 showed the ED95 (effective) dose of hyperbaric bupivacaine for cesarean delivery to be 11.2 mg and 12.6 mg, respectively.…”

Epidural administration of 2% Mepivacaine after spinal anesthesia does not prevent intraoperative nausea and vomiting during cesarean section: A prospective, double-blinded, randomized controlled trial

“…reduce the incidence of IONV. [7] Particularly, intrathecal fentanyl has been reported to effectively improve the quality of regional anesthesia. [1,[8][9][10][11][12][13] However, opioid use causes several complications including pruritus [7][8][9][10]12] , and accidental opioid overdose.…”

“…[7] Particularly, intrathecal fentanyl has been reported to effectively improve the quality of regional anesthesia. [1,[8][9][10][11][12][13] However, opioid use causes several complications including pruritus [7][8][9][10]12] , and accidental opioid overdose. [14][15][16][17] In addition, intrathecal fentanyl was reported to cause acute opioid tolerance.…”